A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

NCT ID: NCT00131963

Last Updated: 2016-07-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 94 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2014-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well doxorubicin, cyclophosphamide, and/or paclitaxel work in treating women with nonmetastatic breast cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the pharmacogenomics of adjuvant chemotherapy comprising doxorubicin and cyclophosphamide and/or paclitaxel in women with nonmetastatic invasive breast cancer.
• Determine treatment-induced myelosuppression (e.g., neutropenia) in patients treated with adjuvant doxorubicin and cyclophosphamide who have polymorphisms in drug activation and metabolism genes.
• Correlate the incidence of peripheral neuropathy with pharmacogenomic analysis in patients treated with paclitaxel.

Secondary

• Determine response (i.e., relapse in the adjuvant setting) during a 10-year follow-up period in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients receive treatment on The Cancer and Leukemia Group B study(CALGB) CALGB-40101 OR are assigned to receive 1 of 2 treatment regimens on this study.

• Regimen 1: Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
• Regimen 2: Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.

After completion of study treatment, patients are followed at 3, 6, and 12 months and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 500 patients (300 treated with doxorubicin and cyclophosphamide and 200 treated with paclitaxel) will be accrued for this study within 3-4 years.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Regimen 1

Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.

cyclophosphamide

Intervention Type: DRUG

Given IV

doxorubicin

Intervention Type: DRUG

Given IV

Regimen 2

Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.

cyclophosphamide

Intervention Type: DRUG

Given IV

doxorubicin

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

Interventions

cyclophosphamide

Given IV

Intervention Type: DRUG

doxorubicin

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

Other Intervention Names

Cytoxan; adriamycin; taxol

Eligibility Criteria

Exclusion Criteria

• Other anticancer cytotoxic or endocrine therapy, immunotherapy, or biologic response modifiers,Study Drugs or other concomitant medications known to cause myelosuppression especially neutropenia and neuropathy
• Eastern Cooperative Oncology Group Performance Status(ECOG) functional status > 2.
• Serious co-morbidities including poorly controlled diabetes mellitus, ischaemic heart disease,uncontrolled hypertension or active infection.
• Pregnancy
• Use of growth factor during cycle 1 of chemotherapy (AC) under pharmacokinetic evaluation
• Grade >/=2 peripheral neuropathy symptoms based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scale. Exception: a chronic neurologic disorder will be reviewed on a case by case basis by the study PI.
• Prior treatment with weekly paclitaxelDISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:

• Node negative disease AND meets 1 of the following stage criteria:

• Primary tumor > T1c
• Primary tumor > T1b AND poor prognostic features, defined as the following:

• High-grade disease
• Human Epidermal Growth Factor Receptor 2 (HER2)/neu-positive disease by fluorescence in situ hybridization
• Estrogen receptor-negative disease
• Stage II disease (T2, N0)
• Node positive nonmetastatic disease
• Locally advanced disease AND receiving neoadjuvant chemotherapy comprising doxorubicin and cyclophosphamide OR paclitaxel
• Enrolled in clinical trial CALGB-40101
• No evidence of systemic metastasis
• Hormone receptor status:

• Not specified

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul K. Marcom, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

Other Identifiers

DUMC-4522-04-1-R1

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000438673

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00014267

Identifier Type: -

Identifier Source: org_study_id